Malignant tumors are among the greatest health problems of man as well as animals, being one of the most common causes of death, also among young individuals. Available methods of treatment of cancer are quite limited, despite intensive research efforts during several decades. Although curative treatment, usually surgery in combination with chemotherapy and/or radiotherapy, is sometimes possible, malignant tumors still require a huge number of lives every year. In fact, curative treatment is rarely accomplished if the disease is not diagnosed early. In addition, certain tumor types can rarely, if ever, be cured.
There are various reasons for this very undesirable situation, the most important one clearly being the fact that most treatment schedules, except surgery, lack sufficient selectivity. Chemotherapeutic agents commonly used do not act on the malignant cells of the tumors alone but are highly toxic to other cells as well, especially to rapidly dividing cell types, such as hematopoietic and epithelial cells, resulting in highly undesirable side effects. The same applies to radiotherapy.
Additionally, short circulation half-life in plasma, limited aqueous solubility, and non-selectivity are usually encountered by most of the currently available anticancer drugs and thus restrict their therapeutic efficacy (Adv. Drug Deliver. Rev. 2002;54:695-713). In addition, two major problems plague the non-surgical treatment of malignant solid tumors. Physiological barriers within tumors impede the delivery of therapeutics at effective concentrations to all cancer cells, and acquired drug resistance resulting from genetic and epigenetic mechanisms reduces the effectiveness of available drugs.
Also in the diagnosis of cancer and of metastases, including the follow-up of patients and the study of the effects of treatment on tumors and metastases, reliable, sensitive and more selective methods and agents would be a great advantage. All methods currently in use, such as nuclear magnetic resonance imaging, X-ray methods, histological staining methods still lack agents that are capable of targeting an entity for detection specifically or selectively to tumor tissues, metastases or tumor cells and/or to tumor endothelium.
Therefore, there is a continuing need in the art for new diagnostic and prognostic methods as well as methods and compositions to allow for cancer targeting and to improve management of patient care.